tbuckley/cabot-search huggingface dataset:
Targeting the Metabolic Enzyme PGAM2 Overcomes Enzalutamide Resistance in Castration-Resistant Prostate Cancer by Inhibiting BCL2 Signaling
Authors: Zhen Li, Kang Ning, Diwei Zhao, Zhaohui Zhou, Junliang Zhao, Xingbo Long, Zhenyu Yang, Dong Chen, XinYang Cai, Lexuan Hong, Luyao Zhang, Fangjian Zhou, Jun Wang, Yonghong Li
Journal: Cancer Research (2023)

The next-generation androgen receptor (AR) inhibitor enzalutamide is the mainstay treatment for metastatic prostate cancer. Unfortunately, resistance occurs rapidly in most patients, and once resistance occurs, treatment options are limited. Therefore, there is an urgent need to identify effective targets to overcome enzalutamide resistance. Here, using a genome-wide CRISPR-Cas9 library screen, we found that targeting a glycolytic enzyme, phosphoglycerate mutase PGAM2, significantly enhanced the sensitivity of enzalutamide-resistant prostate cancer cells to enzalutamide both in vivo and in vitro. Inhibition of PGAM2 together with enzalutamide treatment triggered apoptosis by decreasing levels of the antiapoptotic protein BCL-xL and increasing activity of the proapoptotic protein BAD. Mechanistically, PGAM2 bound to 14-3-3ζ and promoted its interaction with phosphorylated BAD, resulting in activation of BCL-xL and subsequent resistance to enzalutamide-induced apoptosis. In addition, high PGAM2 expression, which is transcriptionally regulated by AR, was associated with shorter survival and rapid development of enzalutamide resistance in patients with prostate cancer. Together, these findings provide evidence of a nonmetabolic function of PGAM2 in promoting enzalutamide resistance and identify PGAM2 inhibition as a promising therapeutic strategy for enzalutamide-resistant prostate cancer.
Validating a model for predicting breast cancer and nonbreast cancer death in women aged 55 years and older
Authors: Emily A Wolfson, Mara A Schonberg, A Heather Eliassen, Kimberly A Bertrand, Yurii B Shvetsov, Bernard A Rosner, Julie R Palmer, Andrea Z LaCroix, Rowan T Chlebowski, Rebecca A Nelson, Long H Ngo
Journal: JNCI Journal of the National Cancer Institute (2023)

To support mammography screening decision making, we developed a competing-risk model to estimate 5-year breast cancer risk and 10-year nonbreast cancer death for women aged 55 years and older using Nurses' Health Study data and examined model performance in the Black Women's Health Study (BWHS). Here, we examine model performance in predicting 10-year outcomes in the BWHS, Women's Health Initiative-Extension Study (WHI-ES), and Multiethnic Cohort (MEC) and compare model performance to existing breast cancer prediction models.
Catalytic Tunable Black Phosphorus/Ceria Nanozyme: A Versatile Oxidation Cycle Accelerator for Alleviating Cisplatin‐Induced Acute Kidney Injury
Authors: Xin Gao, Bei Wang, Jingjing Li, Biao Niu, Lingzhi Cao, Xing‐jie Liang, Jinchao Zhang, Yi Jin, Xinjian Yang
Journal: Advanced Healthcare Materials (2023)

Oxidative stress is one leading inner cause of acute kidney injury (AKI) induced by cisplatin (DDP). Therefore, inhibiting oxidative stress is an important strategy to prevent the occurrence of DDP-induced AKI. Herein, a pH-selective "oxidative cycle accelerator" based on black phosphorus/ceria catalytic tunable nanozymes (BP@CeO2 -PEG) to effectively and persistently scavenge ROS for alleviating DDP-induced AKI is demonstrated. The BP@CeO2 -PEG nanozymes show pH-dependent multi-enzymatic activities, which are beneficial for selectively scavenging the excess ROS in renal tissues. In the neutral environment of kidneys, BP@CeO2 -PEG nanozymes can accelerate its catalytic "oxidative cycle" by increasing the ratio of Ce3+ /Ce4+ and improving the regeneration of ATP, effectively removing DDP-induced ROS. In addition, BP@CeO2 -PEG nanozymes can suppress the oxidative stress-triggered renal tubular epithelial cell apoptosis by inhibiting the PI3K/Akt signaling pathway. However, in the acidic environment of cancers, the presence of H+ inhibits the conversion of Ce4+ to Ce3+ , which in turn disrupts the oxidative cycle, resulting in the loss of ROS scavenging ability and ensuring the antitumor effect of DDP. Conclusively, the nanozymes offer an excellent antioxidant for alleviating cisplatin-induced AKI and extensive use in other ROS-based injuries.
Navigating chimeric antigen receptor-engineered natural killer cells as drug carriers via three-dimensional mapping of the tumor microenvironment
Authors: Shigao Huang, Fuqiang Xing, Yeneng Dai, Zhiming Zhang, Guangyu Zhou, Shuo Yang, Yu-Cheng Liu, Zhen Yuan, Kathy Qian Luo, Tianlei Ying, Dafeng Chu, Tzu-Ming Liu, Chu-Xia Deng, Qi Zhao
Journal: Journal of Controlled Release (2023)
Stargazers
Authors: David Haosen Xiang
Journal: JAMA Oncology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Financial Outcomes of “Bagging” Oncology Drugs Among Privately Insured Patients With Cancer
Authors: Ya-Chen Tina Shih, Ying Xu, James Ching Yao
Journal: JAMA Network Open (2023)

This cohort study examines the difference in per-patient per-month costs between drugs distributed under “bagging,” a drug delivery model that requires patients to obtain physician-administered medications via pharmacies, and traditional buy-and-bill practice.
Celebrating the third World Field Epidemiology Day: a focus on MediPIET the field epidemiology training programme in Mediterranean and Black Sea countries
Authors: Aleksandar Obradovic
Journal: Eurosurveillance (2023)

Preview this article: Celebrating the third World Field Epidemiology Day: a focus on MediPIET the field epidemiology training programme in Mediterranean and Black Sea countries, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/28/36/eurosurv-28-36-1-1.gif
Hospital-Diagnosed Infections, Autoimmune Diseases, and Subsequent Dementia Incidence
Authors: Janet Janbek, Thomas Munk Laursen, Niels Frimodt-Møller, Melinda Magyari, Jürgen G. Haas, Richard Lathe, Gunhild Waldemar
Journal: JAMA Network Open (2023)

Systemic inflammation has been suggested to explain reported associations between infections and dementia. Associations between autoimmune diseases and dementia also suggest a role for peripheral systemic inflammation.To investigate the associations of infections and autoimmune diseases with subsequent dementia incidence and to explore potential shared signals presented by the immune system in the 2 conditions.This nationwide, population-based, registry-based cohort study was conducted between 1978 and 2018 (40-year study period). All Danish residents born 1928 to 1953, alive and in Denmark on January 1, 1978, and at age 65 years were included. Persons with prior registered dementia and those with HIV infections were excluded. Data were analyzed between May 2022 and January 2023.Hospital-diagnosed infections and autoimmune diseases.All-cause dementia, defined as the date of a first registered dementia diagnosis after age 65 years in the registries. Poisson regression with person-years at risk as an offset variable was used to analyze time to first dementia diagnosis.A total of 1 493 896 individuals (763 987 women [51%]) were followed for 14 093 303 person-years (677 147 [45%] with infections, 127 721 [9%] with autoimmune diseases, and 75 543 [5%] with dementia). Among individuals with infections, 343 504 (51%) were men, whereas among those with autoimmune diseases, 77 466 (61%) were women. The dementia incidence rate ratio (IRR) following any infection was 1.49 (95% CI, 1.47-1.52) and increased along with increasing numbers of infections in a dose-dependent manner. Dementia rates were increased for all infection sites in the short term, but not always in the long term. The dementia IRR following any autoimmune disease was 1.04 (95% CI, 1.01-1.06), but no dose-dependent increase was observed, and only a few autoimmune conditions showed increased IRRs for dementia.These findings may point toward a role for infection-specific processes in the development of dementia, rather than general systemic inflammation, as previously hypothesized. Assessing these 2 conditions in a single setting may allow for additional insights into their roles in dementia and for hypotheses on possible underlying mechanisms.
Incorporation of Shared Decision-Making in International Cardiovascular Guidelines, 2012-2022
Authors: Blair J. MacDonald, Ricky D. Turgeon
Journal: JAMA Network Open (2023)

Importance Shared decision-making (SDM) is a key component of the provision of ethical care, but prior reviews have indicated that clinical practice guidelines seldom promote or facilitate SDM. It is currently unknown whether these findings extend to contemporary cardiovascular guidelines. Objective To identify and characterize integration of SDM in contemporary cardiovascular guideline recommendations using a systematic classification system. Design, Setting, and Participants This cross-sectional study assessed the latest guidelines or subsequent updates that included pharmacotherapy recommendations and were published between January 2012 and December 2022 by the American College of Cardiology (ACC), Canadian Cardiovascular Society (CCS), and European Society of Cardiology (ESC). Data were analyzed from February 21 to July 21, 2023. Main Outcomes and Measures All pharmacotherapy recommendations were identified within each guideline. Recommendations that incorporated SDM were rated according to a systematic rating framework to evaluate the quality of SDM incorporation based on directness (range, 1-3; assessing whether SDM was incorporated directly and impartially into the recommendation’s text, with 1 indicating direct and impartial incorporation of SDM into the recommendation’s text) and facilitation (range, A-D; assessing whether decision aids or quantified benefits and harms were provided, with A indicating that a decision aid quantifying benefits and harms was provided). The proportion of recommendations incorporating SDM was also analyzed according to guideline society and category (eg, general cardiology, heart failure). Results Analyses included 65 guideline documents, and 33 documents (51%) incorporated SDM either in a general statement or within specific recommendations. Of 7499 recommendations, 2655 (35%) recommendations addressed pharmacotherapy, and of these, 170 (6%) incorporated SDM. By category, general cardiology guidelines contained the highest proportion of pharmacotherapy recommendations incorporating SDM (86 of 865 recommendations [10%]), whereas heart failure and myocardial disease contained the least (9 of 315 recommendations [3%]). The proportion of pharmacotherapy recommendations incorporating SDM was comparable across societies (ACC: 75 of 978 recommendations [8%]; CCS: 29 of 333 recommendations [9%]; ESC: 67 of 1344 recommendations [5%]), with no trend for change over time. Only 5 of 170 SDM recommendations (3%) were classified as grade 1A (impartial recommendations for SDM supported by a decision aid), whereas 114 of 170 recommendations (67%) were grade 3D (SDM mentioned only in supporting text and without any tools or information to facilitate SDM). Conclusions and Relevance In this cross-sectional study across guidelines published by 3 major cardiovascular societies over the last decade, 51% of guidelines mentioned the importance of SDM, yet only 6% of recommendations incorporated SDM in any form, and fewer adequately facilitated SDM.
A standardised protocol for relative SARS-CoV-2 variant severity assessment, applied to Omicron BA.1 and Delta in six European countries, October 2021 to February 2022
Authors: Tommy Nyberg, Peter Bager, Ingrid Bech Svalgaard, Dritan Bejko, Nick Bundle, Josie Evans, Tyra Grove Krause, Jim McMenamin, Joël Mossong, Heather Mutch, Ajibola Omokanye, André Peralta-Santos, Pedro Pinto-Leite, Jostein Starrfelt, Simon Thelwall, Lamprini Veneti, Robert Whittaker, John Wood, Richard Pebody, Anne M Presanis
Journal: Eurosurveillance (2023)

Several SARS-CoV-2 variants that evolved during the COVID-19 pandemic have appeared to differ in severity, based on analyses of single-country datasets. With decreased testing and sequencing, international collaborative studies will become increasingly important for timely assessment of the severity of new variants. Therefore, a joint WHO Regional Office for Europe and ECDC working group was formed to produce and pilot a standardised study protocol to estimate relative case-severity of SARS-CoV-2 variants during periods when two variants were co-circulating. The study protocol and its associated statistical analysis code was applied by investigators in Denmark, England, Luxembourg, Norway, Portugal and Scotland to assess the severity of cases with the Omicron BA.1 virus variant relative to Delta. After pooling estimates using meta-analysis methods (random effects estimates), the risk of hospital admission (adjusted hazard ratio (aHR) = 0.41; 95% confidence interval (CI): 0.31−0.54), admission to intensive care unit (aHR = 0.12; 95% CI: 0.05−0.27) and death (aHR = 0.31; 95% CI: 0.28−0.35) was lower for Omicron BA.1 compared with Delta cases. The aHRs varied by age group and vaccination status. In conclusion, this study demonstrates the feasibility of conducting variant severity analyses in a multinational collaborative framework and adds evidence for the reduced severity of the Omicron BA.1 variant.
GPT-4 in breast cancer combat: a dazzling leap forward or merely a whim?
Authors: Linfang Deng, None Yangzhang, Shaoting Luo, Jinjiang Xu
Journal: International Journal of Surgery (2023)

aDepartment of Nursing, Jinzhou Medical University, Jinzhou, Liaoning, 121000, PR, China bDepartment of Breast Surgery, Xingtai People's Hospital of Hebei Medical University, Xingtai, Hebei, 054000, PR, China cDepartment of Pediatric Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110000, PR, China dDepartment of Health Management Center, The First Hospital of Jinzhou Medical University, Jinzhou, Liaoning, 121000, PR, China Assistance with the study: The authors would like to acknowledge the contributions of Jinling Zhang. We are also grateful for the technical assistance provided by Qianna Fang. Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. *Corresponding author. Address: First Affiliated Hospital of Jinzhou Medical University, CHINA, Phone: +86 15633941406. E-mail address: [email protected] (J. Xu). Supplemental Digital Content is available for this article. Direct URL citations are provided in the HTML and PDF versions of this article on the journal's website, www.lww.com/international-journal-of-surgery. Published online ■ ■ This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/
Interlocus Gene Conversion, Natural Selection, and Paralog Homogenization
Authors: Yixuan Yang, Tanchumin Xu, Gavin Conant, Hirohisa Kishino, Jeffrey L Thorne, Xiang Ji
Journal: Molecular Biology and Evolution (2023)

Abstract Following a duplication, the resulting paralogs tend to diverge. While mutation and natural selection can accelerate this process, they can also slow it. Here, we quantify the paralog homogenization that is caused by point mutations and interlocus gene conversion (IGC). Among 164 duplicated teleost genes, the median percentage of postduplication codon substitutions that arise from IGC rather than point mutation is estimated to be between 7% and 8%. By differentiating between the nonsynonymous codon substitutions that homogenize the protein sequences of paralogs and the nonhomogenizing nonsynonymous substitutions, we estimate the homogenizing nonsynonymous rates to be higher for 163 of the 164 teleost data sets as well as for all 14 data sets of duplicated yeast ribosomal protein-coding genes that we consider. For all 14 yeast data sets, the estimated homogenizing nonsynonymous rates exceed the synonymous rates.
Antibody correlates of protection against Delta infection after vaccination: A nested case-control within the UK-based SIREN study
Authors: Ana Atti, Ferdinando Insalata, Edward J. Carr, Ashley D. Otter, Sarah Foulkes, Mary Y. Wu, Michelle J. Cole, Ezra Linley, Amanda Semper, Tim Brooks, Susan Hopkins, Andre Charlett, Rupert Beale, Victoria Hall
Journal: Journal of Infection (2023)

ObjectivesTo investigate serological correlates of protection against SARS-CoV-2 B.1.617.2 (Delta) infection after two vaccinations.MethodsWe performed a case-control study, where cases were Delta infections after the second vaccine dose and controls were vaccinated, never infected participants, matched by age, gender and region. Sera were tested for anti-SARS-CoV-2 Spike antibody levels (anti-S) and neutralising antibody titres (nAbT), using live virus microneutralisation against Ancestral, Delta and Omicron (BA.1, B.1.1.529). We modelled the decay of anti-S and nAbT for both groups, inferring levels at matched calendar times since the second vaccination. We assessed differences in inferred antibody titres between groups and used conditional logistic regression to explore the relationship between titres and odds of infection.ResultsIn total, 130 sequence-confirmed Delta cases and 318 controls were included. Anti-S and Ancestral nAbT decayed similarly between groups, but faster in cases for Delta nAbT (p = 0.02) and Omicron nAbT (p = 0.002). At seven days before infection, controls had higher anti-S levels (p < 0.0001) and nAbT (p < 0.0001; all variants) at matched calendar time. A two-fold increase in anti-S levels was associated with a 29% ([95% CI 14–42%]; p = 0.001) reduction in odds of Delta infection. Delta nAbT>40 were associated with reduced odds of Delta infection (89%, [69–96%]; p < 0.0001), with additional benefits for titres >100 (p = 0.009) and >400 (p = 0.007).ConclusionsWe have identified correlates of protection against SARS-CoV-2 Delta, with potential implications for vaccine deployment, development, and public health response.
First cases of SARS-CoV-2 BA.2.86 in Denmark, 2023
Authors: Morten Rasmussen, Frederik Trier Møller, Vithiagaran Gunalan, Sharmin Baig, Marc Bennedbæk, Lasse Engbo Christiansen, Arieh Sierra Cohen, Kirsten Ellegaard, Anders Fomsgaard, Kristina Træholt Franck, Nicolai Balle Larsen, Tine Graakjær Larsen, Ria Lassaunière, Charlotta Polacek, Amanda Gammelby Qvesel, Raphael Niklaus Sieber, Lasse Dam Rasmussen, Marc Stegger, Katja Spiess, Man-Hung Eric Tang, Lasse Skafte Vestergaard, Thomas Emil Andersen, Silje Vermedal Hoegh, Rune Micha Pedersen, Marianne Nielsine Skov, Kat Steinke, Thomas Vognbjerg Sydenham, Morten Hoppe, Lene Nielsen, Tyra Grove Krause, Henrik Ullum, Pikka Jokelainen
Journal: Eurosurveillance (2023)

We describe 10 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant BA.2.86 detected in Denmark, including molecular characteristics and results from wastewater surveillance that indicate that the variant is circulating in the country at a low level. This new variant with many spike gene mutations was classified as a variant under monitoring by the World Health Organization on 17 August 2023. Further global monitoring of COVID-19, BA.2.86 and other SARS-CoV-2 variants is highly warranted.
SPECTRO GLIO trial aftermath: Where do we go from here?
Authors: Hui-Kuo G Shu, Hyunsuk Shim
Journal: Neuro-Oncology (2023)

Journal Article SPECTRO GLIO trial aftermath: Where do we go from here? Get access Hui-Kuo G Shu, Hui-Kuo G Shu Department of Radiation Oncology, Emory University School of Medicine, Atlanta, Georgia, USAWinship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia, USA Corresponding Author: Hui-Kuo G. Shu, MD, PhD, Department of Radiation Oncology and Winship Cancer Institute, Emory University School of Medicine, 1701 Uppergate Drive, Room C-5092, Atlanta, GA 30322, USA (hgshu@emory.edu). https://orcid.org/0000-0002-4060-0874 Search for other works by this author on: Oxford Academic PubMed Google Scholar Hyunsuk Shim Hyunsuk Shim Department of Radiation Oncology, Emory University School of Medicine, Atlanta, Georgia, USADepartment of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, Georgia, USADepartment of Biomedical Engineering, Emory University School of Medicine, Atlanta, Georgia, USAWinship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Neuro-Oncology, Volume 26, Issue 1, January 2024, Pages 164–165, https://doi.org/10.1093/neuonc/noad166 Published: 07 September 2023 Article history Published: 07 September 2023 Corrected and typeset: 22 September 2023
Field Epidemiology: Fit for the future
Authors: Susan Hahné, Charlotte Hammer, Alma Tostmann, Jane Whelan, Christopher Williams
Journal: Eurosurveillance (2023)

In recent years, field epidemiologists have embraced rapidly evolving digital tools, data sources and technologies, and collaborated with an ever-growing field of scientific specialisms. The COVID-19 pandemic put field epidemiology under unprecedented demand and scrutiny. As the COVID-19 emergency recedes, it is timely to reflect on the core values of our profession and the unique challenges and opportunities that lie ahead. In November 2022, alumni of the European Programme for Intervention Epidemiology Training (EPIET) and the European Public Health Microbiology (EUPHEM) training programme celebrated 25 years of EPIET, and the present and future of field epidemiology was discussed. The output was recorded and qualitatively analysed. This Perspective reflects the authors' interpretation of the discussion. We should reaffirm our commitment to field epidemiology's core strengths: competence and rigour in epidemiology, surveillance, outbreak investigation and applied research, leading to timely and actionable evidence for public health. Our future success will be defined by an ability to adapt, collaborate, harness innovation, communicate and, ultimately, by our tangible impact on protecting and improving health.